Capillary basement membrane (BM) thickening characteristic of diabetes has been found in galactosemic rats and evidence for the involvement of aldose reductase (AR) in the process has been documented. In order to test the possible role of this enzyme, two structurally unrelated but similarly potent inhibitors of AR were utilized: sorbinil (Pfizer) and tolrestat (Ayerst). Weanling male SD rats were separated into three groups and fed for 28, 32, and 44 wks: (l) Lab feed (NIH-07); (2) lab feed with galactose (50%); or (3) lab feed with galactose and AR inhibitor (.03% or .04%). Electron micrographs (x25,000) of capillaries from the retina were examined for BM thickness using quantitative computer planimetry on at least 10 capillaries from each of 3-10 rats per dietary group. The BM, cell, and vessel perimeters were traced over graphics tablets and the areas determined with either the NIH DEC 10 or an IBM personal computer using the appropriate digitizing programs. The results were analyzed with the NIH PROPHET computer system. The basement membranes in ocular blood vessels of rats on galactose chow were thicker than those of rats on either control feed or feed containing an AR inhibitor. Up to a two-fold increase in BM thickness occurred in retinal capillaries at 44 weeks. This thickening of BM must be related to AR activity since it did not occur in galactosemic rats (ca. 200 Mug/dl) treated with either sorbinil or tolrestat which are very dissimilar inhibitors. Galactosemic rats shoule be useful models for studying BM-related complications of diabetes and their possible prevention by AR inhibitors.